Efficient synthesis of heterophosphole-2-sulfides by solvent-free microwave reaction

Article abstract of DOI:10.1016/j.tet.2010.08.011

Microwave irradiation of a stoichiometric amount of Lawesson's reagent in the presence of o-aminophenols, o-aminothiophenols, o-phenylenediamines, or catechols leads to benzoxazaphosphole-, benzothiazaphosphole-, benzodiazaphosphole-, and benzodioxaphosphole-2-sulfides, respectively, in good yields in a fast and direct way under solventless conditions. The procedure requires short reaction times and is similar for all reagents; thus it may be used in parallel synthesis.

Full text of DOI:10.1016/j.tet.2010.08.011

Tetrahedron 66 (2010) 8210e8213
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Efficient synthesis of heterophosphole-2-sulfides by solvent-free microwave
reaction
*
*
Julio A. Seijas , M. Pilar Vázquez-Tato , José Crecente-Campo
Dpto. Química Orgánica, Facultad de Ciencias, Universidad de Santiago de Compostela, Aptdo. 280, 27080 Lugo, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 20 July 2010
Received in revised form 2 August 2010
Accepted 5 August 2010
Available online 12 August 2010
Microwave irradiation of a stoichiometric amount of Lawesson’s reagent in the presence of o-amino-
phenols, o-aminothiophenols, o-phenylenediamines, or catechols leads to benzoxazaphosphole-, ben-
zothiazaphosphole-, benzodiazaphosphole-, and benzodioxaphosphole-2-sulfides, respectively, in good
yields in a fast and direct way under solventless conditions. The procedure requires short reaction times
and is similar for all reagents; thus it may be used in parallel synthesis.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Microwave reactions
Lawesson’s reagent
Heteophosphole-2-sulfides
Solvent-free
1. Introduction
reagent in very short reaction times.20 This led us to study the use
of a microwave protocol to prepare phosphole-2-sulfides under
Organophosphorus compounds are ubiquitous in nature and
have applications in the field of agriculture, medicine, and in-
dustry.1,2 Some of them are important pesticides,3 bactericides,4e6
neat conditions, since this reaction involves a nucleophilic addition
to Lawesson’s reagent followed by the elimination of H2S through
polar mechanisms and, consequently, should be a good candidate
to be promoted by microwaves.21
and antibiotics.4 Phosphorus analogues of
a-pyrones act as HIV
protease inhibitors.7 There exists growing interest in organophos-
phorus heterocyclic compounds since extensive use as pesticides in
agriculture, as stabilizers in polymers and as lubricant oil additives
has been found. Among them, many heterocyclic phosphole de-
rivatives are interesting due to their properties.8e14 Lawesson’s
reagent (1), commonly utilized as a thionating agent,15 has been
used to build anisyl derivatives of phosphole-2-sulfides with het-
eroatoms in positions 1 and 3,16e19 by reaction with catechols, 1,
2-phenylenediamines or o-aminophenols. However, these pro-
cedures require the use of refluxing conditions in different solvents
(acetonitrile, toluene, etc.) and long reaction times, but only low
yields are obtained.
Therefore, in order to prepare benzoxazaphosphole-2-sulfides
6, the reaction of o-aminophenol with Lawesson’s reagent was
used as a model. Both compounds were irradiated with micro-
waves under different conditions, and it was found that the re-
action of o-aminophenol (2a) with a stoichiometric amount
(50 mol %) of Lawesson’s reagent (1) for 1 min at 190 ꢀC, in an open
vessel, led to pure (by 1H NMR) 2-(4-methoxyphenyl)-2,3-dihy-
dro-1,3,2-benzoxazaphosphole-2-sulfide (6a). Further purification
by flash chromatography of the crude reaction yielded 73% of 6a
(Scheme 1, Table 1, entry 1). Higher ratio of Lawesson’s reagent
S
MeO
P S
S P
2. Results
OMe
R3
R2
Z1H
Z2H
R3
R2
Z1
S
1
S
P
OMe
Recently, we have reported the formation of 2-(4-methoxy-
phenyl)-4,4-dimethyl-1,3,2-thiazaphospholidine-2-sulfide as an
intermediate in the preparation of thiazolidines under microwave
irradiation from 2-aminoalcohols, carboxylic acids, and Lawesson’s
MW
Z2
R1
R1
6a-c, Z1=O, Z2=NH
7a-b, Z1=S, Z2=NH
8a-d, Z1=NH, Z2=NH
9a-c, Z1=O, Z2=O
2a-c, Z1=O, Z2=NH
3a-b, Z1=S, Z2=NH
4a-d, Z1=NH, Z2=NH
5a-c, Z1=O, Z2=O
* Corresponding authors. Tel.: þ34 982824062; fax: þ34 982285872; e-mail
Scheme 1.
addresses: julioa.seijas@usc.es(J.A. Seijas), pilar.vazquez.tato@usc.es (M.P. Vázquez-Tato).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.08.011

J.A. Seijas et al. / Tetrahedron 66 (2010) 8210e8213
8211
conditions is remarkable (24 and 8%,22 respectively, Table 1, en-
tries 6 and 7).
Table 1
Synthesis of benzoxazaphosphole-, benzothiazaphosphole-, benzodiazaphosphole-,
and benzodioxaphosphole-2-sulfides by microwave irradiation
In the light of these results, the reaction of Lawesson’s reagent
with catechols under irradiation with microwaves was also studied.
The corresponding 1,3,2-benzodioxaphosphole-2-sulfides 9aec
were obtained (Table 1, entries 10e12), with an astounding re-
duction in reaction times as well as an increase in previously
reported yields19 for compounds 9a,b (Table 1, entries 10 and 11).
In order to explore the reactivity of o-quinones with Lawesson’s
reagent, 2,4-di-tert-butyl-1,6-benzoquinone 10 was tested in the
conditions previously described, giving 1,3,2-benzodioxaphosp-
hole-2-sulfide 9c, the same as that obtained from reaction of the
catechol 5c, in 74% yield. No thionation23 of the carbonyl groups of
the quinone was observed (Table 1, entry 13). The formation of
compound 9c may be envisaged to take place through a [4þ2] cy-
cloaddition followed by sulfur extrusion (Scheme 2), instead of
a nucleophilic attack from the oxygen atom on the dithiophosphine
ylide 11, as it is the case for catechols.
Entry Reactant Z1
Z2
R1
R2
R3
Product Yield
Yield
MW (%) reflux (%)a
1
2
3
4
5
6
7
8
2a
2b
2c
3a
3b
4a
4b
4c
4d
5a
5b
5c
10
O
O
O
S
NH
NH
NH
NH
NH
H
H
H
H
H
H
H
H
H
H
Cl
H
Cl
H
H
6a
73
100
93
100
86
68
64
80
73
622
Me 6b
H
H
H
H
H
H
Cl
H
H
6c
7a
7b
8a
8b
8c
8d
9a
9b
3218
S
NH NH
NH NH
NH NH
NH NH
O
O
O
O
2422
822
Me
Cl
Cl
H
7222
9
H
H
10
11
12
13
O
O
O
O
77
74
3219
4819
H
tBu
H
tBu
tBu
tBu 9c
tBu 9c
64
74
H
a
Yields reported in the literature under conventional conditions (refluxing in
toluene or xylene and 50 or 100 mol % of Lawesson’s reagent).
S
S
produced by-products, while with lower Lawesson’s reagent ratio
the yield decreased, as expected. Moreover, shorter reaction
times gave lower yields; while longer ones did not lead to yield
improvement.
MeO
MeO
P
P
S
OMe
tBu
S
1
tBu
tBu
t Bu
tBu
The reaction was also studied under conventional heating in
the same conditions (open tube at 190 ꢀC for 1 min), providing
after chromatography a slightly lower yield of 6a (68% vs 73%). As
several commercial setups for monomode microwave ovens only
allow carrying out reactions in sealed vessels, the above micro-
wave reaction was checked in a sealed vessel. Analysis of the 1H
NMR spectrum of the raw reaction showed unreacted starting
materials and some signals that were not present in the NMR of the
crude for reaction in open vessel, obtaining only a 53% yield after
purification. Analogous results were obtained when the reaction
was carried out under conventional conditions in a sealed tube
(58% yield). This indicated the lack of a specific microwave effect,
since in conventional and microwave reactions yields and times
are comparable. Despite this similarity, we consider that the best
method for the synthesis of heterophosphole-2-sulfides is by
means of microwave irradiation in an open vessel since the yields
are high and the reaction conditions are easier to control. Finally,
a mixture of 1 and 2a was refluxed in toluene for 30 min by irra-
diation with microwaves, after purification a 46% yield of 6a was
obtained; meanwhile 6a was previously prepared by conventional
refluxing for 3 h in the same solvent in only 6% yield.22 The use of
solvent is expendable affording even lower yields than solventless
conditions.
The scope of the reaction was examined by using substituted o-
aminophenols. The reaction of 2-amino-5-methylphenol and 2-
amino-4-chlorophenol led to even higher yields, 100% and 93%, of
benzoxazaphosphole-2-sulfides 6b and 6c, respectively (Table 1,
entries 2 and 3). Azaphosphole 6c had been previously reported in
a 32% yield by refluxing the corresponding aminophenol with
Lawesson’s reagent in toluene.18
These results prompted us to explore the reactivity of 2-ami-
nothiophenols. So, under the same reaction conditions, 2-amino-
benzenethiol (3a) led to the corresponding 1,3,2-benzothiazap
hosphole-2-sulfide 7a quantitatively (Table 1, entry 4). Similarly,
the reaction of 2-amino-4-chlorobenzenethiol (3b) with Law-
esson’s reagent led to the corresponding phosphorus heterocycle
7b in an 86% yield (Table 1, entry 5).
O
P
O
O
S
S
O
O
S
P
S
O
P
S
S
tBu
10
11
9c
OMe
OMe
Scheme 2.
3. Conclusion
In summary, a new, fast, and direct method for the prepara-
tion of heterophosphole-2-sulfides was developed by reacting
a stoichiometric amount of Lawesson’s reagent with different
2-aminophenols, 2-aminothiophenols, 1,2-phenylenediamines, and
catechols. The method was successfully applied for the preparation,
under microwave irradiation in an open vessel and neat reaction
conditions, of a wide variety of compounds, which might be valuable
as potential antibacterials.24 An alternative mechanism is proposed
for the obtention of 4,6-di-tert-butyl-2-(4-methoxyphenyl)-1,3,
2-benzodioxaphosphole-2-sulfide (9c), when an o-quinone is used
instead of the corresponding catechol. Among the compounds de-
scribedhere, onlyone(6c) hadbeen reported as fullycharacterized in
the literature. An advantage of this procedure is the very short re-
actiontimes, whicharesimilarforall reagents, and, thus, maybeused
in parallel synthesis.
4. Experimental section
4.1. General
Melting points were measured in open capillaries and are un-
corrected. 1H NMR spectra were recorded at 300 MHz (1H) and
75 MHz (13C) in the solvent specified (Varian Mercury 300). Mass
spectra were recorded in a low-resolution spectrometer (Hew-
lettePackard 1100 MSD) or high resolution when stated (Micromass
Autospec). Infrared spectra were measured on FT-IR instrument (ABB
BOMEN MB102). Irradiation was carried out in a monomode oven
Discover, CEM Corp. Elemental analysis was performed on a LECO
CHNS-932.
Analogously, 1,2-phenylenediamines reacted with Lawesson’s
reagent in the same conditions described above, yielding the
corresponding 1,3,2-benzodiazaphosphole-2-sulfides in good
yields (Table 1, entries 6e9). The improvement over previously
reported yields for compounds 8a and 8b under conventional

8212
J.A. Seijas et al. / Tetrahedron 66 (2010) 8210e8213
4.2. General procedure
53.23; H, 4.12; N, 4.77; S, 21.86. Found: C, 52.85; H, 3.87; N, 4.84; S,
21.65.
4.2.1. Synthesis of 2,3-dihydro-2-(4-methoxyphenyl)-1,3,2-benzox-
azaphosphole-2-sulfide (6a). A mixture of 2-aminophenol (2a)
(109 mg, 1 mmol) and Lawesson’s reagent (1) (206 mg, 0.51 mmol)
was irradiated in an open vessel with microwaves in a monomode
oven (300 W and temperature control set at 190 ꢀC measured with
an IR sensor) for 1 min.25 The crude was dissolved in dichloro-
methane (1 mL) and purified by short column chromatography
(silica gel, AcOEtehexane, 2:8) giving 6a (202mg, 73%), asa solid. Mp
125e126 ꢀC. IR (Golden-Gate): 3314, 1595, 1484, 1236, 1115, 821, 747,
4.2.5. 5-Chloro-2-(4-methoxyphenyl)-2,3-dihydro-1,3,2-benzothia-
zaphosphole 2-sulfide (7b). Mp 159e161 ꢀC (MeOH). IR (Golden-
Gate): 3323,1589,1581,1427,1250,1105, 918, 800, 702 cmꢁ1.1H NMR
(300 MHz, CDCl3)
d
3.85 (s, 3H, OCH3), 6.30 (d,1H, NH, JPH¼12.3 Hz,),
6.80 (dd,1H, ArH, J¼8.3, 2.0 Hz), 6.85 (d,1H, ArH, J¼2.0 Hz), 6.93 (dd,
2H, ArH, J¼8.9, JPH¼3.5 Hz), 7.08 (d, 1H, ArH, J¼8.3 Hz), 7.94 (dd, 2H,
ArH, JPH¼15.5, J¼8.9 Hz). 13C NMR (75 MHz, CDCl3)
d 55.8 (OCH3),
112.9 (d, JPC¼12.2 Hz, CAr), 114.1 (d, JPC¼16.9 Hz, CAr), 121.3 (d,
JPC¼1.2 Hz, CAr), 121.6 (CAr), 125.1 (d, JPC¼6.7 Hz, CAr), 128.1 (d,
JPC¼117.5 Hz, CAr), 132.2 (d, JPC¼1.2 Hz, CArN), 134.1 (d, JPC¼15.4 Hz,
CAr),140.9 (d, JPC¼6.3 Hz, CArS),163.6 (d, JPC¼3.3 Hz, COCH3). MS m/z
(%):329 (Mþþ2, 41), 328 (Mþþ1,16), 327 (Mþ, 96), 294 (56), 245(31),
188 (100), 140 (29), 63 (36). Anal. Calcd for C13H11ClNOPS2: C, 47.63;
H, 3.38; N, 4.27; S, 19.56. Found: C, 47.69; H, 3.44; N, 4.65; S, 19.17.
704 cmꢁ1.1H NMR (300 MHz, CDCl3)
d 3.85 (s, 3H, OCH3), 5.25 (d,1H,
NH, JPH¼17.7 Hz), 6.84e7.03 (m, 6H, ArH), 7.87 (dd, 2H, ArH,
JPH¼15.1; J¼8.9 Hz).13C NMR (75 MHz, CDCl3)
d 50.9 (OCH3),106.8 (d,
JPC¼11.1 Hz, CAr),107.8 (d, JPC¼9.0 Hz, CAr),109.4 (d, JPC¼17.0 Hz, CAr),
116.5 (CAr), 118.7 (CAr), 121.1 (d, JPC¼145 Hz, CAr), 129.0 (d,
JPC¼15.1 Hz, CAr), 129.3 (d, JPC¼1.5 Hz, CArN), 141.5 (d, JPC¼2.0 Hz,
CArO), 159.1 (d, JPC¼3.1 Hz, COCH3). MS m/z (%): 279 (Mþþ2, 18), 277
(Mþ, 100), 244 (31), 140 (47), 138 (89), 108 (56), 63 (32). Anal. Calcd
for C13H12NO2PS: C, 56.31; H, 4.36; N, 5.05; S,11.56. Found: C, 55.99;
H, 4.45; N, 4.82; S, 11.27.
4.2.6. 2-(4-Methoxyphenyl)-2,3-dihydro-1H-1,3,2-benzodiazaphosp-
hole 2-sulfide (8a). Mp 200e202 ꢀC (CHCl3). IR (Golden-Gate): 3401,
3293, 1593, 1488, 1381, 1246, 1108, 1012, 882, 744, 688 cmꢁ1. 1H NMR
(300 MHz, CDCl3)
d
3.85 (s, 3H, OCH3), 5.05 (d, 2H, 2ꢂNH,
4.2.2. 2-(4-Methoxyphenyl)-6-methyl-2,3-dihydro-1,3,2-benzox-
JPH¼17.9 Hz), 6.74e6.82 (m, 4H, ArH), 6.92 (dd, 2H, ArH, J¼8.8 Hz,
azaphosphole 2-sulfide (6b). Mp 178e179 ꢀC (CH2Cl2). IR (Golden-
JPH¼3.2 Hz,), 7.92 (dd, 2H, ArH, JPH¼14.9 Hz, J¼8.8 Hz,). 13C NMR
Gate): 3328, 1589, 1500, 1251, 1117, 821, 792, 704 cmꢁ1
.
1H NMR
(75 MHz, CDCl3)
d
55.6 (OCH3), 110.9 (d, JPC¼9.6 Hz, CAr), 113.8 (d,
(300 MHz, CDCl3)
d
2.30 (s, 3H, CH3), 3.85 (s, 3H, OCH3), 5.10 (d, 1H,
JPC¼16.5 Hz, CAr), 120.8 (CAr), 130.0 (d, JPC¼151.0 Hz, CAr), 133.2 (d,
JPC¼5.6 Hz, CArN), 133.9 (d, JPC¼14.9 Hz, CAr), 163.3 (d, JPC¼3.1 Hz,
COCH3). MS m/z (%): 278 (Mþþ2, 7), 277 (Mþþ1, 17), 276 (Mþ, 84),
243 (100), 228 (37), 200 (33), 137 (99), 63 (29). Anal. Calcd for
C13H13N2OPS: C, 56.51; H, 4.74; N, 10.14; S, 11.61. Found: C, 56.44; H,
5.08; N, 10.09; S, 11.36.
NH JPH¼16.8 Hz), 6.71e6.78 (m, 2H, ArH), 6.85 (br s, 1H, ArH), 6.93
(dd, 2H, J¼8.8 Hz; JPH¼3.4 Hz, ArH), 7.87 (dd, 2H, ArH, JPH¼15.0 Hz;
J¼8.8 Hz). 13C NMR (75 MHz, CDCl3)
d 21.4 (CH3), 55.7 (OCH3), 111.2
(d, JPC¼11.0 Hz, CAr), 113.4 (d, JPC¼9.0 Hz, CAr), 114.1 (d, JPC¼17.1 Hz,
CAr), 123.5 (CAr), 125.9 (d, JPC¼145.4 Hz, CAr), 131.3 (CAr), 131.5 (d,
JPC¼7.5 Hz, CAr), 133.8 (d, JPC¼15.1 Hz, CAr), 146.2 (d, JPC¼2.3 Hz,
CArO), 163.8 (d, JPC¼3.3 Hz, COCH3). MS m/z (%): 293 (Mþþ2, 6),
292 (Mþþ1, 16), 291 (Mþ, 85), 258 (52), 183 (60), 152 (100), 108
(42), 63 (41). HRMS Anal. Calcd for C14H14NO2PS, 291.048289.
Found: 291.049123. Anal. Calcd for C14H14NO2PS: C, 57.72; H, 4.84;
N, 4.81; S, 11.01. Found: C, 57.37; H, 4.92; N, 4.84; S, 10.80.
4.2.7. 2-(4-Methoxyphenyl)-5-methyl-2,3-dihydro-1H-1,3,2-benzo-
diazaphosphole 2-sulfide (8b). Mp 193e194 ꢀC (AcOEtehexane). IR
(Golden-Gate): 3400, 3284, 1593, 1499, 1372, 1253, 1108, 885, 799,
688 cmꢁ1 1H NMR (300 MHz, CDCl3)
. d 2.25 (s, 3H, CH3), 3.83 (s,
3H, OCH3), 5.12 (d, 1H, NH, JPH¼17.6 Hz,), 5.21 (d, 1H, NH,
JPH¼18.0 Hz,), 6.56e6.64 (m, 3H, ArH), 6.89 (dd, 2H, ArH, J¼8.9 Hz,
JPH¼3.2 Hz), 7.88 (dd, 2H, ArH, JPH¼14.9 Hz, J¼8.9 Hz,). 13C NMR
4.2.3. 5-Chloro-2-(4-methoxyphenyl)-2,3-dihydro-1,3,2-benzox-
azaphosphole 2-sulfide (6c). Mp 136e139 ꢀC (CH2Cl2). Lit.18
194e196 ꢀC. IR (Golden-Gate): 3319, 1594, 1482, 1171, 1114, 886,
(75 MHz, CDCl3)
d
21.3 (CH3), 55.6 (OCH3), 110.6 (d, JPC¼9.5 Hz,
CAr), 111.7 (d, JPC¼9.5 Hz, CAr), 113.8 (d, JPC¼16.4 Hz, CAr), 120.9
(CAr), 128.5 (d, JPC¼137.2 Hz, CAr), 130.3 (CAr), 130.9 (d, JPC¼5.6 Hz,
CArN), 133.3 (d, JPC¼5.7 Hz, CArN), 133.9 (d, JPC¼14.9 Hz, CAr), 163.2
(d, JPC¼3.2 Hz, COCH3). MS m/z (%): 291 (Mþþ1, 31), 290 (Mþ, 100),
257 (82), 242 (34), 122 (45). Anal. Calcd for C14H15N2OPS: C,
57.92; H, 5.21; N, 9.65; S, 11.04. Found: C, 57.70; H, 5.41; N, 9.74; S,
10.60.
823, 803, 707 cmꢁ1. 1H NMR (300 MHz, CDCl3)
d 3.83 (s, 3H, OCH3),
5.88 (d, 1H, NH, JPH¼18.6 Hz), 6.76e6.79 (m, 2H, ArH), 6.88 (d, 1H,
ArH, J¼8.1 Hz), 6.92 (dd, 2H, ArH, J¼8.9 Hz, JPH¼3.5 Hz), 7.81 (dd,
2H, ArH, JPH¼15.1, J¼8.9 Hz). 13C NMR (75 MHz, CDCl3)
d 55.7
(OCH3), 111.8 (d, JPC¼11.0 Hz, CAr), 113.1 (d, JPC¼8.7 Hz, CAr), 114.2 (d,
JPC¼17.2 Hz, CAr), 120.8 (CAr), 125.1 (d, JPC¼145.2 Hz, CAr), 128.4
(CArCl), 133.9 (d, JPC¼15.3 Hz, CAr), 135.0 (d, JPC¼7.6 Hz, CArN), 144.7
(d, JPC¼2.5 Hz, CArO), 164.1 (d, JPC¼3.2 Hz, COCH3). MS m/z (%): 313
(Mþþ2, 22), 312 (Mþþ1, 12), 311 (Mþ, 71), 172 (83), 140 (85), 108
(100), 63 (62). Anal. Calcd for C13H11ClNO2PS: C, 50.09; H, 3.56; N,
4.49; S, 10.29. Found: C, 49.88; H, 4.01; N, 4.45; S, 10.66.
4.2.8. 5-Chloro-2-(4-methoxyphenyl)-2,3-dihydro-1H-1,3,2-benzo-
diazaphosphole 2-sulfide (8c). Mp 171e173 (CHCl3). IR (Golden-
Gate): 3252, 1592, 1485, 1260, 1105, 840, 796, 678 cmꢁ1 1H NMR
.
(300 MHz, CDCl3)
d
3.83 (s, 3H, OCH3), 5.39 (d, 1H, NH, JPH¼17.9 Hz),
5.53 (d, 1H, NH, JPH¼18.2 Hz), 6.60 (d, 1H, ArH, J¼8.8 Hz), 6.67e6.70
4.2.4. 2-(4-Methoxyphenyl)-2,3-dihydro-1,3,2-benzothiazaphosp-
hole 2-sulfide (7a). Mp 137e139 ꢀC (MeOH). IR (Golden-Gate): 3213,
1589, 1453, 1257, 1102, 1023, 892, 750, 678 cmꢁ1. 1H NMR (300 MHz,
(m, 2H, ArH), 6.89 (dd, 2H, ArH, J¼8.9 Hz, JPH¼3.2 Hz), 7.84 (dd, 2H,
ArH, JPH¼15.0 Hz, J¼8.9 Hz). 13C NMR (75 MHz, CDCl3)
d 55.7
(OCH3), 111.1 (d, JPC¼9.7 Hz, CAr), 111.3 (d, JPC¼9.4 Hz, CAr), 114.0 (d,
JPC¼16.6 Hz, CAr), 120.3 (CAr), 125.5 (CAr), 127.7 (d, JPC¼137.6 Hz, CAr),
131.8 (d, JPC¼5.5 Hz, CArN), 134.0 (d, JPC¼15.2 Hz, CAr), 134.2 (CArN),
163.4 (d, JPC¼3.2 Hz, COCH3). MS m/z (%): 312 (Mþþ2; 51), 311
(Mþþ1; 21), 310 (Mþ,100), 279 (40), 278 (19), 277 (82),171 (38),142
(73). Anal. Calcd for C13H12ClN2OPS: C, 50.25; H, 3.89; N, 9.02; S,
10.32. Found: C, 50.45; H, 4.01; N, 8.88; S, 10.10.
CDCl3)
d
3.85 (s, 3H, OCH3), 5.63 (d, 1H, NH, JPH¼12.2 Hz), 6.84 (ddd,
1H, J¼7.9, 1.2, 0.6 Hz, ArH), 6.90 (dd, 1H, J¼7.7, 1.3 Hz, ArH), 6.94 (dd,
2H, ArH J¼9.0 Hz, JPH¼3.4 Hz), 7.07 (tdd, 1H, ArH, J¼7.7, 1.3, 0.9 Hz),
7.20 (ddd, 1H, ArH, J¼7.9, 1.2, 0.6 Hz), 7.98 (dd, 2H, ArH, JPH¼15.4 Hz,
J¼9.0 Hz,). 13C NMR (75 MHz, CDCl3)
d 55.7 (OCH3), 112.7 (d,
JPC¼12.1 Hz, CAr), 114.0 (d, JPC¼16.8 Hz, CAr), 121.7 (CAr), 123.1 (CAr),
124.7 (d, JPC¼7.1 Hz, CAr), 126.7 (CAr), 128.9 (d, JPC¼117.2 Hz, CAr), 134.0
(d, JPC¼15.2 Hz, CAr), 140.0 (d, JPC¼5.8 Hz, CArS), 163.5 (d, JPC¼3.4 Hz,
COCH3). MS m/z (%): 295 (Mþþ2, 21), 294 (Mþþ1, 33), 293 (Mþ, 100),
260 (73), 245 (31), 154 (89), 125 (31). Anal. Calcd for C13H12NOPS2: C,
4.2.9. 5,6-Dichloro-2-(4-methoxyphenyl)-2,3-dihydro-1H-1,3,2-ben-
zodiazaphosphole 2-sulfide (8d). Mp 208e210 ꢀC. IR (Golden-Gate):
3259, 3244,1589,1483,1258,1179,1103, 884, 840, 682 cmꢁ1.1H NMR

J.A. Seijas et al. / Tetrahedron 66 (2010) 8210e8213
8213
(300 MHz, CDCl3)
d
3.85 (s, 3H, OCH3), 5.44 (d, 2H, NH, JPH¼18.0 Hz),
49), 375 (MþꢁCH3; 100), 319 (6), 211 (9), 108 (5), 91 (5), 77 (5), 58
(10), 57 (12). Anal. Calcd for C21H27O3PS: C, 64.59; H, 6.97; S, 8.21.
Found: C, 64.32; H, 7.04; S, 8.05.
6.79 (br s, 2H, ArH), 6.92 (dd, 2H, ArH, J¼8.9 Hz, JPH¼3.3 Hz), 7.84 (dd,
2H, ArH, JPH¼15.0 Hz, J¼8.9 Hz). 13C NMR (75 MHz, CDCl3)
d 55.7
(OCH3), 112.0 (d, JPC¼9.3 Hz, CAr), 114.0 (d, JPC¼16.7 Hz, CAr), 123.4
(CAr),127.3 (d, JPC¼133.4 Hz, CAr),132.8 (d, JPC¼5.8 Hz, CArN),134.0 (d,
JPC¼15.2 Hz, CAr), 163.6 (d, JPC¼3.2 Hz, COCH3). MS m/z (%): 346
(Mþþ2, 75), 346 (Mþþ1, 2), 344 (Mþ, 100), 313 (65), 311 (85), 205
(44), 176 (35). Anal. Calcd for C13H11Cl2N2OPS: C, 45.23; H, 3.21; N,
8.12; S, 9.29. Found: C, 44.87; H, 3.50; N, 7.69; S, 9.66.
Acknowledgements
XUNTA DE GALICIA for financial support: INCITE09 262346PR.
USC for a predoctoral fellowship to J.C.-C., and to Dr. JoDee Ander-
son (Project PGIDIT07-PXID263100PR and English Language, Lit-
erature & Identity Network: 2007/145, Xunta de Galicia) for her
linguistic support.
4.2.10. 2-(4-Methoxyphenyl)-1,3,2-benzodioxaphosphole
(9a). Mp 86e88 ꢀC (hexane). IR (Golden-Gate): 1597, 1479, 1263,
1230, 1122, 868, 777, 742, 719 cmꢁ1 1H NMR (300 MHz, CDCl3)
3.85 (s, 3H, OCH3), 6.95 (dd, 2H, ArH, J¼8.9 Hz, JPH¼3.7 Hz),
2-sulfide
.
Supplementary data
d
Spectra (1H NMR and 13C NMR) of all products are provided.
Supplementary data for this article can be found in the online
version, at doi:10.1016/j.tet.2010.08.011. These data include MOL
files and InChIKeys of the most important compounds described in
this article.
7.01e7.07 (m, 2H, ArH), 7.07e7.16 (m, 2H, ArH), 7.82 (dd, 2H, ArH,
JPH¼15.0 Hz, J¼8.9 Hz). 13C NMR (75 MHz, CDCl3)
d 55.8 (OCH3),
112.8 (d, JPC¼10.3 Hz, CAr), 114.4 (d, JPC¼17.5 Hz, CAr), 122.8 (d,
JPC¼149.6 Hz, CAr), 123.8 (CAr), 133.9 (d, JPC¼15.2 Hz, CAr), 146.0 (s,
C
AreO) 164.5 (d, JPC¼3.5 Hz, COCH3). MS m/z (%): 279 (Mþþ1, 6),
278 (Mþ, 42), 155 (32), 139 (C6H4O2Pþ, 100), 92 (26), 63 (33), 52
(20). Anal. Calcd for C13H11O3PS: C, 56.11; H, 3.98; S, 11.52. Found: C,
55.86; H, 4.11; S, 11.82.
References and notes
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Wiley: New York, NY, 1996; Vol. 4, pp 653e729.
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4.2.11. 5-tert-Butyl-2-(4-methoxyphenyl)-1,3,2-benzodioxaphosp-
hole 2-sulfide (9b). Oil. IR (Golden-Gate): 2964, 1597, 1502, 1491,
1261, 1227, 1121, 920, 864, 806 cmꢁ1 1H NMR (300 MHz, CDCl3)
.
d
1.32 (s, 9H, C(CH3)3), 3.85 (s, 3H, OCH3), 6.96 (dd, 2H, ArH,
J¼9.0 Hz, JPH¼3.7 Hz), 7.00e7.07 (m, 2H, ArH), 7.16 (br s, 1H, ArH),
7.84 (dd, 2H, ArH, JPH¼15.0 Hz, J¼9.0 Hz). 13C NMR (75 MHz, CDCl3)
6. Hendlin, D.; Stapley, E. O.; Jackson, M.; Wallick, H.; Miller, A. K.; Wolf, F. J.;
Miller, T. W.; Chaiet, L.; Kahan, F. M.; Foltz, E. L.; Woodruff, H. B.; Mata, J. M.;
Hernandez, S.; Mochales, S. Science 1969, 166, 122e123.
d
31.7 (C(CH3)3), 35.1 (C(CH3)3), 55.8 (OCH3), 110.3 (d, JPC¼10.0 Hz,
CAr), 111.9 (d, JPC¼9.9 Hz, CAr), 114.4 (d, JPC¼17.4 Hz, CAr), 120.2 (CAr),
122.9 (d, JPC¼148.0 Hz, CAr), 134.0 (d, JPC¼15.2 Hz, CAr), 143.6 (CArO),
145.7 (CArO),147.7 (CArC(CH3)3),164.4 (d, JPC¼3.3 Hz, COCH3). MS m/
z (%): 335 (Mþþ1, 9), 334 (Mþ, 47), 319 (Mþ, 100), 211 (12), 139 (9),
58 (13). Anal. Calcd for C17H19O3PS: C, 61.06; H, 5.73; S, 9.59. Found:
C, 61.01; H, 6.04; S, 9.10.
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12. Neda, I.; Melnicky, C.; Vollbrecht, A.; Schmutzler, R. Synthesis 1996, 473e474.
13. Viljanen, T.; Taehtinen, P.; Pihlaja, K.; Fueloep, F. J. Org. Chem. 1998, 63, 618e627.
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An, W.; Yu, Z.; Hong-Wei, H. Chinese J. Struct. Chem. 2005, 10, 1211e1216.
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4.2.12. 4,6-Di-tert-butyl-2-(4-methoxyphenyl)-1,3,2-benzodiox-
aphosphole 2-sulfide (9c). Mp 134e135 ꢀC (CH2Cl2). IR (Golden-
Gate): 2962, 1593, 1410, 1261, 1121, 972, 864 cmꢁ1 1H NMR
.
(300 MHz, CDCl3)
d 1.33 (s, 9H, C(CH3)3), 1.42 (s, 9H, C(CH3)3), 3.85
19. Shabana, R.; Osman, F. H.; Atrees, S. S. Tetrahedron 1994, 50, 6975e6988.
20. Seijas, J. A.; Vázquez-Tato, M. P.; Crecente-Campo, J. Tetrahedron 2008, 64,
9280e9285.
(s, 3H, OCH3), 6.97 (dd, 2H, ArH, J¼8.8 Hz, JPH¼3.6 Hz), 7.03 (s, 2H,
ArH), 7.86 (dd, 2H, ArH, JPH¼15.0 Hz, J¼8.8 Hz). 13C NMR (75 MHz,
CDCl3)
d 29.8 (C(CH3)3), 31.8 (C(CH3)3), 34.8 (C(CH3)3), 35.2 (C
21. Perreux, L.; Loupy, A. Tetrahedron 2001, 57, 9199e9223.
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24. Shen, X. Q.; Liu, H. L.; Zhang, H. Y.; Zhang, H. Q.; Mao, H. Y.; Wu, Q. A.; Zhu, Y.;
Hou, H. W. Chinese J. Struct. Chem. 2005, 24, 1211e1216.
(CH3)3), 55.7 (OCH3), 108.1 (d, JPC¼10.2 Hz, CAr), 114.3 (d,
JPC¼17.3 Hz, CAr), 117.5 (CAr), 123.4 (d, JPC¼148.0 Hz, CAr), 133.9 (d,
JPC¼15.1 Hz, CAr), 135.3 (d, JPC¼8.1 Hz, CAr), 141.6; 145.9; 146.7 (CAr),
164.3 (d, JPC¼3.3 Hz, COCH3). MS m/z (%): 391 (Mþþ1; 12), 390 (Mþ,
25. For dioxaphospholes (9aec) the reaction time was 5 min.